1. Field of the Invention
The present invention relates generally to the fields of organic chemistry, medical bacteriology and medical mycology. More specifically, the present invention relates to the identification of antibacterial and antifungal flavanones.
2. Description of the Related Art
Flavanoids, a wide-spread group of water-soluble phenolic derivatives in plants, are structurally based on the flavan moiety and consist of two aromatic rings joined in a chroman structure by a three carbon unit (C.sub.6 -C.sub.3 -C.sub.6). ##STR1##
These phenylchroman ring systems include flavanones, flavones, flavanols, flavans, catechins and anthrocyanidins which are classified according to the state of oxidation of the C.sub.3 unit; i.e., corresponding to carbons-2,3,4 in the molecule. The variety of compounds within the flavanoid group results from the hydroxylation of one, two or more of the carbon atoms in rings A and B, especially, carbons 2, 3 and 4 of the flavan structure. The hydroxyl groups may be further glycosylated, acylated, alkylated or isoprenylated.
Modern microbiological techniques have demonstrated that higher plants frequently exhibit significant potency against human bacterial and fungal pathogens and that the compounds isolated and/or subsequently synthesized possess therapeutic potential. A wide variety of flavanoids with prenyl substituents exhibit growth inhibitory activity against several microorganisms. Plants of the legume family (Leguminosae, Fabaceae) are known to produce a variety of bioactive compounds, among them antiinfective, antimicrobial or antibacterial flavanones.
The structure-activity relationship among flavanones indicates that a 2', 6'-or 2', 6'-dihydroxylation of the B ring and a 5, 7-dihydroxylation of the A ring results in significant activity against methicillin-resistant Staphylococcus aureus (MRSA). Substitution with a certain aliphatic group at the 6- or 8- position also enhances the anti-MRSA activity. Among the differently substituted flavanones isolated from Sophora exigua (Leguminosae) and Echinosophora koreensis (Leguminosae) which possessed these structural characteristics, 5,7 ,2',6'-tetrahydroxy-6-isoprenyl-8-lavandulyl-4'-methoxy-flavanone (exiguaflavanone D) and 5,,2',6'-trihydroxy-6-isoprenyl-8-lavandulyl-7-methoxy-flavanone (exiguaflavanone B) had a minimum inhibitory concentration of 1.56-6.25 .mu.g/ml and 50 .mu.g/ml, respectively, for all MRSA strains examined.
Two new isoflavans and the known constituent 2',7-hydroxy-3',4',8-trimethoxyisoflavan (isoduratin) have been isolated from the bark and trunk of Eysenhardtia polystachya (Leguminosae). Spectroscopic analysis identified the unknown isoflavans as (3S)-7-hydroxy-2',3',4',8-pentamethoxyisoflavan and (3S)-3',7-hydroxy-2',4',5',8-tetramethoxyisoflavan. These new compounds along with the isoduratin demonstrated moderate cytotoxic activity against certain cell lines.
The prior art is deficient in any description of biologically active flavanones from desert legumes that are of potential biomedical significance. The present invention fulfills this long-standing need and desire in the art.